Dr. Staudt's laboratory is taking three molecular approaches to understanding the development and function of lymphocytes. The first approach focuses on changes in the expression of transcription factors which take place when hematopoietic stem cells differentiate along the B cell lineage. In particular, Dr. Staudt has studied a novel population of mouse bone marrow progenitor cells which can differentiate, under appropriate conditions, into either B cells or myeloid cells. A variety of transcription factors studied were expressed in both the progenitor and differentiated cells. By contrast, two transcription factors, Oct-2 and LEF-1, were present at low or undetectable levels in the progenitor cells and are strongly induced upon differentiation to the lymphoid, but not the myeloid, lineage. Thus, Oct-2 and LEF-1 may play a role in commitment of a stem cell to the lymphoid lineage. The second approach involves the molecular cloning of novel lymphoid-restricted genes using subtractive hybridization techniques. One such gene, Ly-GDI, encodes a protein bearing striking homology to a regulator of the ras-like GTP- binding protein, rho, and may regulate events during lymphocyte activation. Another protein, JAW-1, has homology to the coiled-coil region of myosin and, surprisingly, resides in the endoplasmic reticulum. Both of these proteins reveal tissue-specific regulation of cellular processes that were previously thought to behave similarly in all cell types. The final approach involves the rapid and large-scale sequencing of cDNAs derived from subtracted and conventional cDNA libraries prepared from normal human lymphocytes or human lymphoid malignancies such as Burkitt's lymphoma and chronic lymphocytic leukemia.